title: Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient.
abstract: OBJECTIVE
  Maraviroc is the first licensed chemokine co-receptor 5 (CCR5) co-receptor antagonist in clinical practice. It is currently being used in patients harbouring exclusively CCR5-tropic virus. The objective of the study was to investigate the impact of maraviroc on viruses with different co-receptor preferences in a patient with a dual/mixed (D/M) infection.
  
  
  METHODS
  We present a case report of an HIV-1 patient infected with a D/M virus population. Co-receptor tropism was determined by phenotypic and genotypic tests. Biological clones from pre- and post-maraviroc therapy were generated. Tropism of these infectious clones was investigated in U373-MAGI cells expressing CD4+ CCR5+ or CD4+ CXCR4+. Maraviroc susceptibility and viral replication were determined using donor peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  In-depth clonal genotypic analysis revealed the presence of both R5-tropic variants and X4-tropic viruses before the start of maraviroc. During maraviroc therapy all R5-predicted viruses were suppressed. Phenotypic analyses revealed that all biological clones before maraviroc therapy could infect both CCR5- and CXCR4-bearing U373-MAGI cells, demonstrating dual tropism. The baseline biological clones preferentially infected the CCR5 cell line and were fully susceptible to maraviroc in PBMCs (dual-R5). In contrast, during maraviroc therapy the dual-R5-tropic viruses were replaced by more X4-tropic viruses (dual-X4), which could not be inhibited by maraviroc.
  
  
  CONCLUSIONS
  This case report demonstrates that dual-tropic viruses, capable of using both co-receptors in phenotypic assays, can be inhibited by maraviroc if they have a CCR5 co-receptor preference in vivo.
authors.affiliation: Department of Virology, Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Jori
authors.initials: J
authors.lastname: Symons
authors.forename: Steven F L
authors.initials: SF
authors.lastname: van Lelyveld
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Petra M
authors.initials: PM
authors.lastname: van Ham
authors.forename: Dorien
authors.initials: D
authors.lastname: de Jong
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D003510:Cyclohexanes / Q000008:administration & dosage* / Q000494:pharmacology; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology; D056189:Viral Tropism
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc